Abstract 19063: Risk Stratification for Life-threatening Ventricular Arrhythmias in Lamin A/C Mutation Carriers, Results of an European Registry.
Introduction: Lamin A/C (LMNA) mutations are associated with a variety of clinical phenotypes, most notably cardiomyopathy. Mutation carriers have a poor prognosis because of a high prevalence of both sudden cardiac death and heart failure. It has been suggested that LMNA mutation carriers may benefit from primary implantation of an Implantable Cardioverter-Defibrillator (ICD). However, risk factors identifying individuals at high risk of life-threatening ventricular arrhythmias (VA) have not yet been established. The aim of the present study is to identify such risk factors defining which carriers would benefit the most from primary ICD implantation.
Methods: In this European registry 275 LMNA mutation carriers were followed with a median duration of 46 months (IQR 17–105 months). This allowed us to evaluate risk factors for life-threatening VA, defined as sudden cardiac death, appropriate ICD-treatment or resuscitation.
Results: Of the 275 LMNA mutation carriers, 109 had received an ICD as primary prevention based on individual decisions by the caring physician. Twenty five of 109 carriers who received an ICD for primary prevention received appropriate ICD treatment, resulting in an average of 8 events per 100 person years. In total, life-threatening VA occurred in 48 (17%) mutation carriers. In a multivariate analysis non-sustained ventricular tachycardia, left ventricular ejection fraction < 45%, male gender and ins-del/nonsense/splice site mutations were independent risk factors for life-threatening VA. Importantly, life-threatening VA occurred exclusively in carriers with two or more of these risk factors. For each additional risk factor, the risk for life-threatening VA was cumulative (figure 1).
Conclusion: We identified four independent but additive clinical and genetic risk factors for life-threatening VA in LMNA mutation carriers. This facilitates selection of LMNA mutation carriers who are most likely to benefit from an ICD.
- © 2010 by American Heart Association, Inc.